Reacción #2286318

Ecuación de reacción

[3,5-dichloro-4-(5-isopropyl-6-oxo-1,6-dihydro-pyridazin-3-ylmethyl)-phenyl]-acetonitrile

[3,5-Dichloro-4-(5-isopropyl-6-oxo-1,6-dihydro-pyridazin-3-ylmethyl)-phenyl]-acetonitrile

ethyl acetate

→

acetic acid

Rendimiento 13.0%

[3,5-Dichloro-4-(5-isopropyl-6-oxo-1,6-dihydro-pyridazin-3-ylmethyl)-phenyl]-acetic acid

Rendimiento 13.0%

Disolventes

hydrochloric acid

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturawas heated
2. 2
   Temperaturato reflux for 24 h
3. 3
   Lavadowashed with a saturated aqueous sodium chloride solution (20 mL) and water (10 mL)
4. 4
   Extracciónextracted with ethyl acetate (50 mL)
5. 5
   Secadodried over magnesium sulfate
6. 6
   Filtraciónfiltered
7. 7
   Concentraciónconcentrated under vacuum
8. 8
   OtroThe resulting oil was purified by HPLC (acetonitrile/water with 0.1% trifluoroacetic acid)
9. 9
   OtroThe desired fractions were collected
10. 10
    Concentraciónconcentrated
11. 11
    Otrofreeze dried
12. 12
    OtroThe resulting solid was purified by flash chromatography
13. 13
    Lavadoeluted with 10% methanol in methylene chloride
14. 14
    OtroThe desired fractions were collected
15. 15
    Concentraciónconcentrated under vacuum
16. 16
    Otroto afford a solid which
17. 17
    Otrowas dried under high vacuum

Procedimiento

A mixture of [3,5-dichloro-4-(5-isopropyl-6-oxo-1,6-dihydro-pyridazin-3-ylmethyl)-phenyl]-acetonitrile (55) (assume 0.180 mmol) in concentrated hydrochloric acid (4 mL) was heated to reflux for 24 h. The reaction mixture was cooled to room temperature, diluted with ethyl acetate (75 mL) and washed with a saturated aqueous sodium chloride solution (20 mL) and water (10 mL). The water layers were combined and extracted with ethyl acetate (50 mL). The organic layers were combined, dried over magnesium sulfate, filtered, and concentrated under vacuum. The resulting oil was purified by HPLC (acetonitrile/water with 0.1% trifluoroacetic acid). The desired fractions were collected, concentrated and freeze dried. The resulting solid was purified by flash chromatography using silica gel eluted with 10% methanol in methylene chloride. The desired fractions were collected and concentrated under vacuum to afford a solid which was dried under high vacuum to afford 3,5-dichloro-4-(5-isopropyl-6-oxo-1,6-dihydro-pyridazin-3-ylmethyl)-phenyl]-acetic acid (56) (8.6 mg, 13% for 2 steps) as a white solid; EI(+)-HRMS m/z calcd for C16H16Cl2N2O3 (M+H)+ 355.0611, found 355.0611. MW=355.2235, Exact Mass=354.0538

Fuente